The disruption of the protein complex mutantp53/p73 increases selectively the response of tumor cells to anticancer drugs.
Many in vitro and in vivo evidence have shown that the status of p53 is a key determinant in the response of tumor cells to anticancer treatment. Here we provide evidence that peptide-mediated targeting of the protein complex mutantp53/p73 enhances the response of mutant p53 tumor cells to commonly used anticancer drugs. Indeed, we show that the disruption of the protein complex mutantp53/p73 and the consequent restoration of p73 transcriptional effects, through the activity of short interfering peptides, render mutant p53 cells more prone to the killing of adriamycin and cisplatin. Of note, the activity of the short interfering peptides is mutant p53 specific and causes no effects on wt-p53 and p53 null cells. Our findings highlight the protein complex mutantp53/p73 as a molecular target, whose successful overriding through the selective activity of small interfering peptides, might contribute to the optimization of mutant p53 tumor treatments.
Di Agostino
Silvia
S
Pharmacocinetic and Animal Models Unit, Regina Elena Cancer Institute, Rome, Italy.
Cortese
Giancarlo
G
Monti
Olimpia
O
Dell'Orso
Stefania
S
Sacchi
Ada
A
Eisenstein
Miriam
M
Citro
Gennaro
G
Strano
Sabrina
S
Blandino
Giovanni
G
D000970:Antineoplastic Agents / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000494:pharmacology; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D004317:Doxorubicin / Q000494:pharmacology; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D008954:Models, Biological; D046912:Multiprotein Complexes / Q000378:metabolism*; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D010455:Peptides / Q000494:pharmacology; D011401:Promoter Regions, Genetic; D011485:Protein Binding / Q000187:drug effects; D014158:Transcription, Genetic / Q000187:drug effects; D014161:Transduction, Genetic; D000072160:Tumor Protein p73; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism
D000970:Antineoplastic Agents; D004268:DNA-Binding Proteins; D046912:Multiprotein Complexes; D009687:Nuclear Proteins; D010455:Peptides; C000606460:TP73 protein, human; D000072160:Tumor Protein p73; D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins; D004317:Doxorubicin; D002945:Cisplatin